Novel Circulating Exosomal microRNAs for Early Diagnosis and Prognosis of HCV-Associated Liver Diseases

Abstract

Liver cancers are a major global burden accounting for approximately 782,000 deaths annually. Amongst the various risk factors, hepatitis C virus (HCV) is thought to be responsible for 25% of liver cancers resulting in 350-500,000 deaths annually. Irreversible liver damage resulting in hepatocellular carcinoma (HCC) is often associated with late diagnosis and prognosis. With the current field of research moving towards non-invasive liquid biopsies as opposed to solid biopsies, circulating exosomal miRNAs have received a lot of attention over the years as promising biomarkers for detecting HCV and HCV-associated liver diseases. Although studies in finding novel circulating exosomal miRNAs to improve diagnosis have been successful, a number of key questions still need to be addressed. This paper will explore (i) the current methods for detecting HCV and HCV-associated liver diseases and address their benefits as well as limitations; second, (ii) the promising miRNAs that have been implicated in such diseases and are currently being studied will be examined with supporting literature; and finally, (iii) the obstacles that have slowed the development of using miRNAs as a non-invasive biomarker for HCV-associated liver diseases in a clinical setting will be addressed. This paper will focus on two candidate miRNAs that may be used in clinical settings to detect these diseases. MiRNA-122 is a liver-specific miRNA that is significantly downregulated in HCC and can discriminate between HCC and chronic HCV infection. In contrast, miRNA-500a is significantly upregulated in HCC and has been implicated in preventing the anti-apoptotic activity of Bcl-2 via activation of the BID protein, promoting cancer progression. In the future, the field may move towards developing anti-miRNAs as anticancer agents for disease treatment.